The present invention relates generally to the delivery of a beneficial agent to a patient or into a system for later delivery to a patient. More specifically, the present invention relates to drug delivery systems.
For many applications, drugs are mixed with a diluent before being delivered, for example, intravenously, to a patient. The diluent can be, for example, a dextrose solution, a saline solution, or even water. To this end, many such drugs are supplied in powder form and packaged in glass vials or ampules. Other drugs, such as some chemotherapy drugs, are packaged in glass vials or ampules in a liquid state.
Powdered drugs can be reconstituted by utilizing a syringe to inject liquid into a vial for mixing; the syringe eventually withdrawing the mixed solution from the vial. When a drug must be diluted before delivery to the patient, the drug is often injected into a container of diluent after it is reconstituted; the container can be connected to an administration set for delivery to the patient.
Drugs may be packaged separately from the diluent for various reasons. One of the more important reasons is that many drugs do not retain their chemical and physical stability when mixed with a diluent and thus, cannot be stored for any substantial period of time. Also, drugs are often packaged separately from the diluent because many companies that manufacture drugs are not engaged in the business of providing medical fluids and containers for intravenous delivery and vice versa.
Therefore, a doctor or nurse, a pharmacist, or other medical personnel must mix the drug and diluent. This presents a number of problems. The reconstitution procedure is time consuming and requires aseptic technique. The operator must provide the proper diluent in a syringe before beginning. Often the powdered drug is "caked" at the bottom of the vial. Thus, when liquid is injected into the vial from a syringe, the surface area of contact between the liquid and the powdered drug may be quite small. Initially, this may make the mixing procedure even more time consuming.
Because of the limited vial volume, increasing the drug concentration in the diluent makes it harder to complete the reconstitution process. The operator may attempt to solve this problem by repeatedly injecting solution into the vial, mixing and withdrawing the solution. This attempt to solve the problem makes additional injections and movement of the syringe necessary, increasing the likelihood of contamination. Also, it is sometimes difficult to remove all of the drug and/or liquid from the vial, thus increasing the time required to perform the reconstitution procedure.
The reconstitution procedure should be performed under preferably sterile conditions. This requirement requires the operator to be more cautious, thereby consuming more time. Additionally, sterile conditions are often hard to maintain. In some instances, a laminar flow hood may be required in which the reconstitution procedure is performed. A further concern is that some drugs, such as chemotherapy drugs, are toxic. Exposure of the operator to the drugs during reconstitution can be dangerous, especially if the operator works with such drugs on a daily basis and is repeatedly exposed to them.
After a drug is reconstituted and withdrawn into a syringe barrel, the drug can, in some instances, be immediately injected into the patient. More typically, however, the reconstituted drug is injected from the syringe into a larger container of solution for connection to an intravenous administration set. A larger container of solution may be necessary because often the reconstituted drug in the syringe is at such a concentration as to cause local toxicity in the veins of a patient near the injection site where the needle pierces the skin. This can create severe vein irritation which can be harmful.
Additionally, even though the proper dose of medication may be in the syringe, immediate injection into the patient's blood stream can create a condition of systemic toxicity wherein the level of drug concentration in the patient's entire blood stream is dangerously high. Yet another reason for not making an injection from the syringe directly into the patient is that such injection creates an additional injection site into the patient; this can be painful to the patient and provides another opportunity for infection.
For these reasons, the reconstituted drug is more typically injected into a diluent container.
There are a variety of examples of drug delivery systems that can be used to deliver drugs to a patient and/or reconstitute a drug. An example of such a system is disclosed in U.S. Pat. No. 4,850,978. The system includes a cartridge for introducing a beneficial agent into a fluid conduit for delivery of the agent to a patient. The cartridge includes a rigid hollow tube and an agent-containing chamber slidably mounted at least partially within the hollow tube. In a first, pre-use position, the chamber extends farther from the hollow tube than it does in a second position. A cannula is mounted to the hollow tube extending opposite the chamber. When the chamber is in the second position, the cannula pierces the closure means creating a fluid flow path.
U.S. Pat. No. 4,804,366 also discloses a drug delivery system including an adaptor having an improved flow path means providing both an inlet and an outlet to the agent-containing chamber of a cartridge. The cartridge and adaptor permit a single opening through the injection sites at opposite ends of the flow path means, while still permitting simultaneous flow both into and out of the chamber. An adaptor in the cartridge is provided, including a rigid cannula with an inlet and an outlet and a shell substantially coaxial with and spaced from the cannula intermediate of the cannula inlet and the cannula outlet, so that the shell of the cannula defines a channel therebetween. Both the cannula inlet and the cannula outlet are adaptable to form a single piercing opening in a resilient injection site associated with the receptacle of the delivery system. Both the channel outlet and cannula inlet are adapted to form a single piercing opening in a resilient injection site associated with the cartridge.
The drug vials and specifically the stoppers may have a variety of different shapes and constructions depending on the composition contained therein. For example, lyophilized and non-lyophilized drug vials have different stopper types. The lyophilized stopper typically has a different geometry than a non-lyophilized stopper. Due to the construction of the lyophilized stopper, certain issues may be raised. For example, the geometry of the lyophilized stopper will require the cannula to accurately pierce the center of the lyophilized stopper. Missing the stopper target, or center of the lyophilized stopper, and entering the vial on an angle can result in an occluded vial inlet flow path and thereby a failure of the drug delivery device to deliver the dose (stop flow).
Another issue with respect to drug vial stoppers is the inconsistency or lack of lubrication. In a drug delivery device such as those set forth above, insufficient stopper lubrication can result in the stopper resisting cannula penetration. Once the user releases the pressure used to pierce the stopper, the vial can "spring back" thereby preventing total cannula penetration. The result can be an occluded flow path, i.e., stop flow.